Behavioral effects of alpha-alkylated amino acid analogs in the C57BL/6J mouse

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Although a series of amino acid analogs have been shown to modulate brain function, information on the pharmacology of alpha-alkylated amino acids (AAAA) is limited. In particular there is no information on the effect of these amino acid analogs (AAA) on the elevated plus maze, the tail suspension test and the forced swim test. It was therefore the aim of the study to test a series of AAAA in these paradigms in order to explore behavioral activities of this compound class.

10 male mice per group aged between 10 and 14 weeks were used. Vehicle-treated controls were used in addition to intraperitoneal injections of 1, 10 and 100 mg/kg body weight of each, alpha-amino-isobutyic acid (AIB), isovaline (IVA), alpha-propyl-alanine (APA), alpha-butyl-alanine (ABA), alpha-pentyl-alanine (APnA), alpha-ethylphenylglycine (AEPG) and alpha-methyl-valine (AMV). The elevated plus maze (EPM), the tail suspension test (TST) and forced swim test (FST) were used for behavioral testing.

There were dose-dependent results: all compounds increased time and pathlength in the open arm of the EPM at least at one dose administered. In the TST and in the FST only the 100 mg dose was showing an effect.

The results show pharmacological activity modifying the EPM in low doses suggesting the use in treatment of behavioral traits and symptoms represented by or linked to the EPM including anxiety-related behavior including depression. Compounds acting at higher doses may be used to induce behavioral changes and thus serve as neurobiological-neuropharmacological tools.

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